Curcumin and its therapeutic analogs (Curcuma rhizomes, extracts, Curcuminoids (desmethoxycurcumin, bisdesmethoxycurcumin, tetrahydrocurcumin), prodrugs and metabolites) have been shown to exhibit various pharmacological activities such as anti-oxidant and antiproliferative properties, induction of apoptosis, etc. Based on in vitro results, Curcumin offers the potential to act as a drug for the treatment of pathologies described in the state of the art such as psoriasis, cancer, inflammatory processes, vitiligo, etc.
Curcumin and its equivalents reportedly exhibit very low oral bioavailability. Br J. Cancer. 2004 Mar. 8; 90(5):1011-5 discloses that after oral administration, only trace levels of its metabolites were found in liver tissue, and no curcumin was found. Therefore, an artisan would presume that Curcuminoids lack in vivo efficacy following oral administration, and efficacy is much reduced in vivo as compared to in vitro results. J Am Acad Dermatol. 2008 April; 58(4):625-31 corroborates this finding (published after priority date). The document reports that a phase II, uncontrolled trial in patients older than 18 years who were orally administered 4.5 g Curcuminoids/day had to be abandoned because only 17% of patients responded to treatment with a reduction of 75% of psoriatic plaque.
Due to the demonstrated lack of efficacy following oral administration, an artisan of skill, such as cited in Amand et al Biochem Pharmacol. 2008 Aug. 19. [Epub ahead of print] (published after priority dated), would be motivated to search for solutions for improving in vivo efficacy of Curcumin oral formulations and to discover a “supercurcumin”, if such a compound was available. Solutions to the lack of oral efficacy that have been found include, for example, structural modifications for improving Curcumin absorption (EP1837030), new galenic formulations (WO/2008/030308), and the administration of high doses in combination of other active ingredients (U.S. Pat. No. 5,925,376, WO03088986).
Phototherapy is a useful tool for treatment of various diseases such as proliferative and/or dermatological pathologies (psoriasis, cancer), acne and jaundice. Phototherapy activity is based on the structural changes in compounds induced by the radiation. Phototherapy is used for the treatment of jaundice in newborn. The newborn, having a body surface area of 0.20 m2, is irradiated with visible light, preferably with an emission maximum at 550 nm, and an irradiance close to 40 W/m2 in order to degrade bilirubin.
Actinic light (maximum emission at 420 nm) is used for acne treatment based on its bactericide properties. The surface area irradiated by these lamps is less than 400 cm2.
Photochemotherapy, concomitant administration of psoralens and irradiation with ultraviolet light, is the treatment of choice for moderate to severe psoriasis, but the treatment has many secondary effects: hyperpigmentation, hepatotoxicity, hypersensitization reactions. Sivanesan et al. (J. Am. Acad. Dermatol. (2009), 61, 793-8) discloses the results of a clinical study on the efficacy of UVA radiation alone as compared to UVA radiation in combination with orally administered psoralen capsules in the treatment of psoriasis. Even after 12 weeks, the UVA radiation alone did not reduce in any patient the PASI score by 75% in the psoriasis area. Moreover, the irradiated dose must be carefully adjusted in order to minimize the carcinogenic property of UV radiation.
Aminolevulinic acid combined with blue light phototherapy has been shown to be effective in the treatment of actinic keratosis. J Invest Dermatol. 2002 July; 119(1):77-83 describes its systemic administration (oral) in combination with 1-20 J/cm2 visible light (LED (light emitting diode)—maximum emission at 417 nm) for the treatment of psoriasis, but the efficacy is limited and said treatment cannot be used in moderate to severe psoriasis. The results obtained showed that on 15 plaques of 1.5*1.5 cm (34 cm2) the severity of the plaques was only improved by 42% compared to baseline.
In in vitro assays and trials employing topical administration, photoradicals or degradants generated in situ by irradiation are unstable and are those responsible for pharmacological activity. Photosensitization after the administration of a photosensitizing agent administered systemically cannot be produced immediately; the drug must first be metabolized and, later, must be photoactivated. In summary, effectiveness of phototherapy cannot be predicted a priori, because it depends on bioavailability of the drug administered and on pharmacological activity of artifacts formed during the irradiation.
In the particular case of Curcumin, the state of the art shows that it has very low bioavailability, and further, it is known that Curcuminoids are degraded by visible-ultraviolet light, both in solution and solid state. The major degradation product is a cyclization of Curcumin by loss of 2 hydrogen atoms.
Psoriasis is a chronic disease and its etiology is not fully understood. Clinically, psoriasis is characterized by the of presence patches or erythematosus plaques with a dark reddish color, delimited borders and often covered with scales that are due to the changes in cellular proliferation marked by genetic and immunological mechanisms. Thus, psoriasis may be considered as a proliferative disease.
The severity of psoriasis is determined by the PASI index (Psoriasis Area Severity Index), BSA (Body Surface Area) and PGA (Physican Global Assessment). PASI is an objective index and is used to evaluate drug therapeutic efficacy. According to PGA, psoriasis may be classified into:                Mild or moderate psoriasis: lesions are under control with topical treatment; BSA<10%, PASI<10,        Moderate psoriasis: it is still possible to control the disease with topical treatment; BSA>10%, PASI 10 or higher,        Moderate to Severe psoriasis: topical treatment cannot control the disease; BSA>10%, PASI 10-20; very thick lesions in areas that are difficult to treat,        Severe psoriasis: systemic treatment necessary to control the disease; BSA>20%, or PASI>20; important local lesions of high thickness with BSA>10%.        
EMEA Guidelines criteria establish that patients are considered responders when PASI reduction is at least 75% of the baseline.
Currently, there is no widely accepted animal model to assess the in vivo efficacy of pharmaceuticals in the treatment of psoriasis. Drug efficacy must be tested in people who suffer from psoriasis or in animal models by studying inhibition of tumor proliferation, for example, the cell proliferation of the A431 cell line (cells of epidermal carcinoma).
Efalizumab, recently authorized for psoriasis treatment, has some efficacy. In 12 week studies, 22-35% of patients reached a score of PASI-75 (improvement of 75%).
Photochemotherapy with Aminolevulinic acid and visible light only showed 42% improvement in psoriatic plaques compared to baseline. According to EMEA guidelines, the treatment lacks effectiveness, in particular in the treatment of moderate to severe and severe psoriasis.
Psoriasis patients tend to hide their lesions and often abandon topical treatments, because these stain clothes. In accordance with an opinion poll conducted by European Federation of Psoriasis Associations, there is a high degree of dissatisfaction in psoriasis sufferers regarding the efficacy of such treatments for this disease and they give up treatment.
EP1133992 describes the photosensitizing activity of visible-UV light on Curcuminoids, administered in the form of a topically applied extract, for the treatment of psoriasis. The cream described in EP1133992 must be applied before the radiation, but the treatment is abandoned by patients because the Curcuma extracts are colored and stain clothes. Moderate to severe psoriasis that involves more than 10% of body surface area cannot be treated by the topical route because the patients do not respond to treatments administered via the topical route. The '992 patent discloses irradiation of cultured human keratinocytes with UV radiation (UVA range 340-390 nm, UVB range 290-310 nm, 150 mJ/cm2 or 1 J/cm2), and the irradiation of psoriatic skin in human patients using visible light (weekly sessions of irradiation with a 440 nm lamp (radiation intensity unspecified) with 3 min irradiation periods).
The results obtained in phototherapy by the topical administration route cannot be extrapolated to systemic administration as described for aminolevulinic acid.
Another type of phototherapy currently being used is photodynamic therapy. The drug is administered and the patients irradiated with a pulsed light having a high irradiance of approximately 300 mW/cm2. The light is administrated on a small surface for short time interval, irradiating 100 J/cm2, but the method causes pain to patients.
Exemplary phototherapy devices currently available include:                UV-Cabins emitting an irradiance of 2-30 mW/cm2 of ultraviolet light over the whole body surface area of the patient, but without emitting visible light,        devices emitting visible light irradiating a small surface area of approximately 500 cm2, but always less than 10% body surface area of an adult, and        Gas Discharge Lamps having an emission range of 400-550 nm and which may be fitted to UV-cabins, for example, Phillips TLK 40 W/03 or TLK 140 W/03 but these lamps are used for photo printing and for aquarium lighting.        
There are also filters for selectively absorbing certain wavelengths and transmitting radiations of 400-430 nm.
Given that to date no drug has shown efficacy in phototherapy with visible light following oral administration of the drug, artisans in the field would not be motivated to combine the low intensity radiation equipment described above in order to manufacture a phototherapy device that emits visible light having an irradiance higher than 2 mW/cm2 over a surface greater than 0.2 m2 or greater than 40 cm2, wherein the device can be used to treat psoriasis, cancer, tumor, vitiligo or other disorder or disease.